Search PubMed⌕ Search

Biomedical subjects

M A Friedman

Publications and source records attributed to M A Friedman.

211 records · Page 12Linked to original sources
PubMedDate not supplied

Pharmacokinetics of benzophenone-3 after oral exposure in male rats.

Benzophenone-3 (BZ-3) is one of the UV-absorbing agents that has been used in industry and medicine for more than 30 years. Millions of consumers are exposed to benzophenones on a daily basis owing to the widespread use of these compounds in many of the products on the market, such as lipsticks, hair sprays, hair dyes, shampoo and detergent bars and sunscreen lotions. This study was performed to investigate the pharmacokinetics of BZ-3 after oral administration at 100 mg kg-1 body weight in male Sprague-Dawley rats. Absorption from the gastrointestinal tract was rapid because BZ-3 was detected in blood 5 min after administration. The peak plasma concentration (Cmax) was 25.6 +/- 4.6 micrograms ml-1 and the time of occurrence (tmax) was 3.0 +/- 0.4 h. The half-life of absorption of BZ-3 was 0.71 h. The elimination pattern was biphasic with alpha and beta half-lives of elimination of 0.88 and 15.90 h, respectively. The results of this study indicate the presence of strong binding between the plasma protein and BZ-3. Tissue distribution studies at 6 h indicate that the liver contained the highest concentration of free (58.9 +/- 23.8 micrograms) and total (free+bound or conjugated) BZ-3 (2087 +/- 60.1 micrograms), followed by kidney and testes, respectively. Urine and feces analysis indicate that urine was the major route of excretion, followed by feces. Further analysis of urine samples also indicates that conjugation of BZ-3 with glucuronic acid was the major systemic elimination route for the compound.

Administration, Oral↗
PubMedDate not supplied

Potential pooling opportunities: cancer.

The pooling of large amounts of clinical data from all available and relevant (diverse) sources in order to achieve greater statistical confidence may be appropriate for most modern and well conducted clinical investigations. However, in order to arrive at specific and meaningful conclusions, such exercises absolutely depend upon the homogeneity (or at least comparability) of the study population and therapy under scrutiny. There are currently many opportunities for pooling studies of cancer treatment. The most attractive disease situations are those with a sufficiently large number of completed randomized studies. Some to be considered are colon cancer, gastric cancer, hepatoma, ovarian cancer and lymphoma.

Clinical Trials as Topic↗
PubMedDate not supplied

Self-directed hostility and family functioning in normal-weight bulimics and overweight binge eaters.

The aim of this study was to examine whether overweight binge eaters demonstrate similar perceptions of family interactions and views of the self as do normal-weight bulimics. We compared 37 obese binge eaters and 37 normal-weight bulimics to 38 normal-weight non-bulimic controls, and 10 overweight nonbulimic controls on the Bulimia Test (BULIT). Profile of Mood States (POMS), Structural Analysis of Social Behavior (SASB) Short Form, which includes measure of hostility of family interactions and self-directed hostility; the Family Interaction Survey (FIS), and a measure of history of physical and sexual abuse and familial psychopathology. Both normal-weight bulimics and overweight binge eaters differed from nonbulimic controls across all measures of symptomatology, family functioning, history of abuse, familial psychopathology, and self-directed hostility. Normal-weight bulimics demonstrated significantly higher BULIT scores and self-directed hostility than did overweight binge eaters. Post hoc analysis showed that among binge eaters and bulimics, self-directed hostility accounted for a significant percentage of the variance of BULIT scores when controlling for the effects of age, BMI, family hostility, and mood. The possible role of self-directed hostility in the maintenance of bulimic symptomatology is discussed.

Adult↗
PubMedDate not supplied

Relationship between acrylamide reproductive and neurotoxicity in male rats.

To determine whether there is a relationship between the reproductive and neurotoxic effects of acrylamide monomer (AM), the first week of the study design of Sublet et al. ¿14 was duplicated: Long-Evans male rats were gavaged with AM in water, 25/group, at 0, 5, 15, 30, 45, or 60 mg/kg/day for 5 days (days 1 through 5). On Day 8, males were paired overnight with untreated virgin females (1 : 1) in proestrus/estrus. On day 9, males were evaluated for forelimb and hindlimb grip strength. Five males/group were perfusion fixed, 20/group were used for andrologic assessment, and all were necropsied. Perfusion-fixed sciatic nerves were examined histologically. Sperm-positive females were examined for preimplantation and postimplantation loss at midpregnancy. At 15 to 60 mg/kg/day, males exhibited significantly reduced weight gain, reduced mating, fertility, and pregnancy indices by trend analysis (significant at 60 mg/kg/d by pairwise comparison), and increased postimplantation loss and dominant lethal factor, F(L)%, at 45 and 60 mg/kg/day. At 60 mg/kg/day, the sperm beat cross frequency was increased, with no significant effects on epididymal sperm motility or concentration, and hindlimb grip strength was decreased, with no pathologic lesions in sciatic nerves. Therefore, epididymal sperm, mating, and neurotoxic effects were observed at AM doses that also resulted in increased postimplantation loss, possibly by different mechanisms.

Acrylamide↗
PubMedDate not supplied

Rat two-generation reproduction and dominant lethal study of acrylamide in drinking water.

Fischer 344 (F344) F(0) weanling rats, 30/sex/group, were exposed to acrylamide in drinking water at 0.0, 0.5, 2.0, or 5.0 mg/kg/day for 10 weeks and then mated. Exposure of F(0) females continued through gestation and lactation of F(1) litters. F(0) males, after F(0) mating, were removed from exposure and mated (one male: two untreated females) for the dominant lethal (DL) assay. Thirty F(l) weanlings/sex/group were exposed for 11 weeks to the same dose levels as their parents, and then mated to produce F(2) offspring. F(0) and F(l) parents and F(1) and F(2) weanlings were necropsied. Prebreeding exposure of F(0) and F(l) animals resulted in systemic toxicity at 2.0 to 5.0 mg/kg/day, with head tilt and/or foot splay increased at 0.5 to 5.0 mg/kg/day. F(0) and F(l) reproductive indices and gestational length were unaffected. Implantations and live pups/litter at birth were reduced at 5.0 mg/kg/day. Survival of F(l) and F(2) pups was reduced at 5.0 mg/kg/day for PND 0 through 4 only. In the DL assay, total and live implants were reduced, pre- and postimplantation loss was increased, and the frequency of DL factors (F(L)%) was increased at 5.0 mg/kg/day. At 5.0 mg/kg/day, adult F(l) male peripheral nerves exhibited axonal fragmentation and/or swelling; F(l) female spinal cord sections were unremarkable. The NOEL for prenatal DL was 2.0 mg/kg/day; the NOEL for adult systemic toxicity, including neurotoxicity, was < or = 0.5 mg/kg/day. Therefore, neurotoxicity and DL were differentially affected.

Acrylamide↗
PubMedDate not supplied

Effects of lactational administration of acrylamide on rat dams and offspring.

We duplicated the study design of Husain et al. (Ind Health 1987; 25:19-28) to determine whether maternal exposure to acrylamide monomer (AM) resulted in offspring neurotoxicity. Wistar rat dams with litters (15/group) were gavaged with AM in saline at 0 or 25.0 mg/kg/d throughout lactation (pnd 0-21). Maternal feed and water consumption, body weights (BW), and Functional Observational Battery (FOB) were recorded. At weaning (pnd 21), maternal sciatic nerves were examined histologically. Male offspring were retained until pnd 91, with BW and grip strength evaluations. Dosed dams exhibited progressive toxicity, including mortality (two), severely reduced feed and water consumption, BW, and BW gain, and behavioral neurotoxicity (with no sciatic nerve pathology). Nursing offspring at 25.0 mg/kg/d exhibited increased mortality and reduced BW associated with little/no milk in stomachs. Postwean males at 25.0 mg/kg/d exhibited normal BW gain and increasing grip strength over time. Therefore, AM caused maternal toxicity; offspring effects during lactation were consistent with inanition from maternal toxicity. Postwean males exhibited recovery with no signs of AM-mediated toxicity. These results do not support the conclusions of Husain et al.

Acrylamide↗
PubMedDate not supplied

Therapy for hepatocellular cancer with intrahepatic arterial adriamycin and 5-fluorouracil combined with whole-liver irradiation: a Northern California Oncology Group Study.

Thirteen patients with hepatocellular cancer were treated with intrahepatic arterial Adriamycin and 5-fluorouracil combined with whole-liver irradiation. Six patients (46%) had an objective regression and five (38%) had stable disease. Symptomatic improvement was noted in 81% of the patients. The minimum median survival time was 5.0 months for those patients who responded. Toxicity was acceptable. This is an effective combination for the treatment of this especially aggressive and intractable form of cancer.

Adult↗
PubMedDate not supplied

Effects of N-nitrosodiethylamine on murine hepatic mixed-function-oxidase activities.

Administration of N-nitrosodiethylamine (diethylnitrosamine, DEN) to mice caused a loss of cytochrome P-450 and a corresponding depression in the activities of aminopyrine demethylase and aniline hydroxylase. Maximum effects were achieved 24 hr. after a single dose of 100 mg/kg. In chronic experiments, similar effects were achieved after animals had been drinking water containing 50 ppm of DEN for 12 weeks. The effects of DEN on aminopyrine demethylase could not be reproduced by collecting microsomes, from homogenates which had been treated with DEN in vitro. Homogenates prepared from livers of mice treated chronically with DEN were used to activate compounds to mutagens in the Salmonella/microsome test of Ames. Activation by these homogenates was not lower than activation by homogenates prepared from control animals. In fact, activation of aflatoxin B1 was enhanced by use of homogenates from DEN-treated animals as source of activating enzymes.

Aminopyrine N-Demethylase↗
PubMedDate not supplied

Phase II study of sequential methotrexate and 5-FU plus mitomycin and leucovorin in patients with disseminated large bowel cancer: a Northern California Oncology Group study.

Sequential methotrexate (MTX) and 5-FU plus leucovorin and mitomycin (MMC) was given to 52 patients with disseminated, measurable colorectal cancer. Complete and partial responses were seen in 19 of 49 (39%) evaluable patients. Nine additional patients achieved a minimal response. Median overall survival was 8.8 months, while that for patients objectively responding was 13.6 months. This study utilized a MTX exposure period of 12 hours prior to 5-FU. In comparison to other trials utilizing sequential MTX and 5-FU, the addition of MMC to the regimen may improve the response rate but increases the incidence of adverse effects, particularly myelosuppression and renal toxicity. This phase II trial suggests that sequential MTX and 5-FU plus leucovorin and MMC is an active combination therapy and warrants further comparative trial in patients with large bowel cancer.

Adult↗
PubMedDate not supplied

Metabolism of benzophenone-3 in rats.

Benzophenone-3 [2-hydroxy-4-methoxybenzophenone (HMB), oxybenzone, Spectra-Sorb UV-9 light absorber] is used in many cosmetics and sunscreens as a UV absorber. This study was conducted to investigate the metabolism of HMB (100 mg/kg body weight administered orally). 2,4-Dihydroxybenzophenone (DHB), 2,2'-dihydroxy-4-methoxybenzophenone (DHMB), and 2,3,4-trihydroxy-benzophenone (THB) metabolites were identified as free and conjugated forms by HPLC analysis. HMB was rapidly absorbed, metabolized, and detected in plasma (as free and protein bound) at 5 min postadministration. The parent compound and metabolites (free and conjugated) were detected at 6 hr in most tissues. DHB was present in most tissues with the highest concentration in the liver. DHMB was only detected as the conjugated form in liver, spleen, and heart. Trace amounts of THB were also detected in biological samples. Urine was the primary route, whereas feces was the secondary route of elimination of HMB and its metabolites. This study revealed O-dealkylation as the major pathway of HMB metabolism.

Animals↗
PubMedDate not supplied

Mesotheliomas of tunica vaginalis testis of Fischer 344 (F344) rats treated with acrylamide: a light and electron microscopy study.

The incidence of spontaneous mesotheliomas of the tunica vaginalis testis, documented to be 1.3% in Fischer 344 rats can be increased by long term exposure to acrylamide. The light microscopic and electron microscopic features of tumors developing spontaneously in control animals were compared with those that developed in acrylamide treated animals to determine whether the tumors in the experimental group have any distinctive characteristics. The experimental group comprised three subgroups, i.e. animals exposed to acrylamide in three doses 0.1, 0.5 or 2.0 mg/kg/day over a period of 104 weeks. A total of 35 tumors were examined--7 in control group, 9 in low-dose group, 8 in mid-dose group and 11 in the high-dose group. Most tumors measured less than 1 cm in diameter in aggregate and approximately one-third of all tumors were of microscopic size, less than 5 mm in diameter. All tumors were classified as epithelial mesotheliomas. Three distinct microscopic patterns were recognized (papillary, tubular or solid). All tumors had papillary features, and focally showed some tubular or solid components. No ultrastructural differences were found between tumors of the four groups of animals. It was concluded that the tumors that developed in the tunica vaginalis testis of acrylamide treated animals do not differ morphologically from those that developed spontaneously in control animals. Cellular uniformity, small size of lesions and the absence of perotoneal seeding and metastasis suggests that the mesotheliomas of tunica vaginalis testis of Fischer 344 rats in this study were benign and equivalent to human benign mesothelioma of tunica vaginalis testis or adenomatoid tumors.

Acrylamide↗